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Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant=\"normal\">x<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">L<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>and proapoptotic Bcl-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant=\"normal\">x<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">S<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>. This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant=\"normal\">x<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">L<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant=\"normal\">x<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">L<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>over Bcl-<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant=\"normal\">x<\/mml:mi><\/mml:mrow><mml:mrow><mml:mi mathvariant=\"normal\">S<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis.<\/jats:p>","DOI":"10.1155\/2016\/7478650","type":"journal-article","created":{"date-parts":[[2016,8,7]],"date-time":"2016-08-07T21:02:32Z","timestamp":1470603752000},"page":"1-7","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells"],"prefix":"10.1155","volume":"2016","author":[{"given":"Lin","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqiong","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 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